Hui Wang1, Yong-Guang Yang. 1. Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York 10032, USA.
Abstract
PURPOSE OF REVIEW: This review assesses the recent progress in xenograft rejection by innate immune responses, with a focus on innate cellular xenoreactivity. RECENT FINDINGS: Current literature was reviewed for new insights into the role of innate cellular immunity in xenograft rejection. Increasing evidence confirms that vigorous innate immune cell activation is accounted for by a combination of xenoantigen recognition by activating receptors, and incompatibility in inhibitory receptor-ligand interactions. Although both innate humoral and cellular xenoimmune responses are predominantly elicited by preformed and induced xenoreactive antibodies in nonhuman primates following porcine xenotransplantation, innate immune cells can also be activated by xenografts in the absence of antibodies. The latter antibody-independent response will likely persist in recipients even when adaptive xenoimmune responses are suppressed. In addition to xenograft rejection by recipient innate immune cells, phagocytic cells within liver xenografts are also deleterious to recipients by causing thrombocytopenia. SUMMARY: Strategies of overcoming innate immune responses are required for successful clinical xenotransplantation. In addition to developing better immunosuppressive and tolerance induction protocols, endeavors towards further genetic modifications of porcine source animals are ultimately important for successful clinical xenotransplantation.
PURPOSE OF REVIEW: This review assesses the recent progress in xenograft rejection by innate immune responses, with a focus on innate cellular xenoreactivity. RECENT FINDINGS: Current literature was reviewed for new insights into the role of innate cellular immunity in xenograft rejection. Increasing evidence confirms that vigorous innate immune cell activation is accounted for by a combination of xenoantigen recognition by activating receptors, and incompatibility in inhibitory receptor-ligand interactions. Although both innate humoral and cellular xenoimmune responses are predominantly elicited by preformed and induced xenoreactive antibodies in nonhuman primates following porcine xenotransplantation, innate immune cells can also be activated by xenografts in the absence of antibodies. The latter antibody-independent response will likely persist in recipients even when adaptive xenoimmune responses are suppressed. In addition to xenograft rejection by recipient innate immune cells, phagocytic cells within liver xenografts are also deleterious to recipients by causing thrombocytopenia. SUMMARY: Strategies of overcoming innate immune responses are required for successful clinical xenotransplantation. In addition to developing better immunosuppressive and tolerance induction protocols, endeavors towards further genetic modifications of porcine source animals are ultimately important for successful clinical xenotransplantation.
Authors: Hui Wang; Maria Lucia Madariaga; Shumei Wang; Nico Van Rooijen; Per-Arne Oldenborg; Yong-Guang Yang Journal: Proc Natl Acad Sci U S A Date: 2007-08-15 Impact factor: 11.205
Authors: Kenneth Cardona; Gregory S Korbutt; Zvonimir Milas; James Lyon; Jose Cano; Wanhong Jiang; Hameeda Bello-Laborn; Brad Hacquoil; Elizabeth Strobert; Shivaprakash Gangappa; Collin J Weber; Thomas C Pearson; Ray V Rajotte; Christian P Larsen Journal: Nat Med Date: 2006-02-26 Impact factor: 53.440
Authors: Robert B Elliott; Livia Escobar; Paul L J Tan; Maria Muzina; Sahar Zwain; Christina Buchanan Journal: Xenotransplantation Date: 2007-03 Impact factor: 3.907
Authors: Bernhard J Hering; Martin Wijkstrom; Melanie L Graham; Maria Hårdstedt; Tor C Aasheim; Tun Jie; Jeffrey D Ansite; Masahiko Nakano; Jane Cheng; Wei Li; Kathleen Moran; Uwe Christians; Colleen Finnegan; Charles D Mills; David E Sutherland; Pratima Bansal-Pakala; Michael P Murtaugh; Nicole Kirchhof; Henk-Jan Schuurman Journal: Nat Med Date: 2006-02-19 Impact factor: 53.440